Joss Whedon went through five different versions of the final battle with the "Newborn" creature, the first four versions of which all took place on Earth in such settings as a hospital maternity ward, a giant junkyard, a snowy forest and cliffside, and a desert.

Jean-Pierre Jeunet originally wanted to cast a woman as the main villain but the studio refused, seeing as the film already had two female leads.

Although it appears that the cast spend most of the time wandering up and down endless spaceship corridors, in reality there were only two built for the film.

As the film progresses, the walls of the ship's corridors become darker and more ominous.

Milk had to be added to the underwater set as the water was simply too transparent to be convincing.

The underwater segment was shot on a specially constructed sound stage on the Fox lot, which was converted into a permanent water-tank. It took nearly a week to fill it with water and three weeks to film in. The actors were subjected to about 15 underwater training sessions in swimming pools around the Los Angeles area before arriving at the underwater set where they underwent a further 2 weeks of training before anything was shot. Sigourney Weaver missed most of this because she had been appearing in a play on Broadway just prior to filming.

The alien eggs were made to appear more vivid and pulsating at the request of director Jean-Pierre Jeunet. After watching Alien, he thought the eggs were too static.

Sigourney Weaver made the behind-the-back half-court basketball shot successfully after two weeks of basketball practice, tutored by a basketball coach. Her conversion rate during that two weeks was about one shot in from every six. When the day came to shoot the scene, director Jean-Pierre Jeunet wanted to have the ball dropped in from above, rather than wait for Weaver to sink the shot herself, which "would probably take about 200 takes". Weaver insisted that the she could get the shot in herself, which she was finally allowed to do. She sunk the shot on the very first take, even though she was six feet further past the three-point line. Ron Perlman was completely stunned (and thoroughly impressed), and turned directly at the camera and broke character, saying, "Oh my God!" The editors looked at the shot and decided that there was "enough room to get the scissors in". Weaver was excited about making the shot, but Jeunet was concerned that audiences would believe the shot to be faked due to the ball leaving the frame. Upon Weaver's insistence, he kept the shot as it was. Weaver described the miracle shot as one of the best moments in her life, after her wedding day and the birth of her daughter, of course.

Winona Ryder nearly drowned during the filming of the underwater scene, as did actor Ron Perlman. At one point, when trying to surface, he hit his head on a sprinkler in the ceiling, knocking him out cold. He was rescued by nearby film crew members.